The overall objectives of this research proposal are to precisely define the metabolic changes and their sequence immediately following the induction of myocardial ischemia. The initial thrust of the project will be studies aimed at determining the effect of ischemically induced changes in the tissue ratio of long chain acyl CoA ester (LCACAE)/carnitine upon the activity of adenine nucleotide translocase (ANT), mitochondrial creatine phosphokinase (M-CPK), carnitine translocase, and related inner membrane-linked mitochondrial enzyme systems. The possible function of acetyl carnitine as the prime energy storage fuel of the ischemic myocardium will be investigated, and further studies on the mechanism by which carnitine protects the ischemic myocardium will be made. These investigations will be made in both dog and rat heart preparations, as well as in isolated mitochondria. Physiological and ultrastructural studies will also be made simultaneously, to more completely describe metabolic change during ischemia. Attempts to isolate, purify and characterize various heart mitochondrial translocating enzymes will be undertaken in an effort to more fully define their role in the regulation of cardiac metabolism.